Effect of cl 184, 005, a platelet-activating factor antagonist in a murine model of staphylococcus aureus-induced gram-positive sepsis

Susan Quinn De Joy, Robert Jeyaseelan, Lawrence W. Torley, Walter C. Pickett, Allan Wissner, Michael M. Wick, Arnold L. Oronsky, S. S. Kerwar

Research output: Contribution to journalArticle

Abstract

Experiments using a murine model of heat-killed Staphylococcus aureus-induced gram-positive bacterial sepsis indicate that the lethal bacterial effects can be prevented if mice are pretreated with CL 184, 005, a platelet-activating factor (PAF) antagonist. CL 184, 005 was ineffective when administered after bacterial challenge. Plasma of mice pretreated with CL 184, 005 contained significantly less tumor necrosis factor (TNF), suggesting that CL 184, 005 interferes with TNF synthesis induced by S. aureus. Spleen-associated TNF protein was also decreased by pretreatment with CL 184, 005. Although TNF levels were significantly decreased in mice treated with CL 184, 005, interleukin-6 levels in serum were significantly increased. Athymic mice were also susceptible to the lethal effects of S. aureus, suggesting that T cells were not involved. When rats rendered hypotensive with S. aureus were treated with CL 184, 005, their blood pressure was normalized. Mice treated with enterotoxin B were not protected if they were pretreated with CL 184, 005; however, TNF levels in these mice were significantly lower, suggesting that mediators other than PAF and TNF may contribute to the lethal effects of enterotoxin.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalJournal of Infectious Diseases
Volume169
Issue number1
DOIs
StatePublished - Jan 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Effect of cl 184, 005, a platelet-activating factor antagonist in a murine model of staphylococcus aureus-induced gram-positive sepsis'. Together they form a unique fingerprint.

  • Cite this

    De Joy, S. Q., Jeyaseelan, R., Torley, L. W., Pickett, W. C., Wissner, A., Wick, M. M., Oronsky, A. L., & Kerwar, S. S. (1994). Effect of cl 184, 005, a platelet-activating factor antagonist in a murine model of staphylococcus aureus-induced gram-positive sepsis. Journal of Infectious Diseases, 169(1), 150-156. https://doi.org/10.1093/infdis/169.1.150